Hypoxia-inducible factors (HIFs) were discovered as activators of erythropoietin gene transcription in response to reduced oxygen (O2) availability. O2-dependent hydroxylation of HIFs on proline and asparagine residues regulates protein stability and transcriptional activity, respectively. Mutations in genes encoding components of the O2-sensing pathway cause familial erythrocytosis. Several small-molecule inhibitors of HIF prolyl hydroxylases are currently in clinical trials as erythropoiesis-stimulating agents. HIFs are overexpressed in bone marrow neoplasms, and the development of HIF inhibitors may improve outcomes in these disorders.
CITATION STYLE
Semenza, G. L. (2022, April 21). Breakthrough science: hypoxia-inducible factors, oxygen sensing, and disorders of hematopoiesis. Blood. Elsevier B.V. https://doi.org/10.1182/blood.2021011043
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